Alpha-glucosidase inhibitory and hypoglycemic effects of imidazole-bearing thioquinoline derivatives with different substituents: In silico, in vitro, and in vivo evaluations.

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by high blood sugar levels. It was shown that modulating the activity of α-glucosidase, an enzyme involved in carbohydrate digestion and absorption, can improve blood sugar control and overall metabolic health in individuals with T2DM. As a result, in the current study, a series of imidazole bearing different substituted thioquinolines were designed and synthesized as α-glucosidase inhibitors. All derivatives exhibited significantly better potency (IC50 = 12.1 ± 0.2 to 102.1 ± 4.9 µM) compared to the standard drug acarbose (IC50 = 750.0 ± 5.0 µM). 8g as the most potent analog, indicating a competitive inhibition with Ki = 9.66 µM. Also, the most potent derivative was subjected to molecular docking and molecular dynamic simulation against α-glucosidase to determine its mode of action in the enzyme and study the complex's behavior over time. In vivo studies showed that 8g did not cause acute toxicity at 2000 mg/kg doses. Additionally, in a diabetic rat model, treatment with 8g significantly reduced fasting blood glucose levels and decreased blood glucose levels following sucrose loading compared to acarbose, a standard drug used for blood sugar control. The findings suggest that the synthesized compound 8g holds promise as an α-glucosidase inhibitor for improving blood sugar control and metabolic health.

Surface functionalization of endotracheal tubes coated with laccase-gadolinium phosphate hybrid nanoparticles for antibiofilm activity and contrasting properties.

Ventilator-associated pneumonia (VAP) is a severe hospital-acquired infection that endangers patients' treatment in intensive care units (ICUs). One of the leading causes of VAP is biofilm formation on the endotracheal tube (ETT) during ventilation. This study reports a combination of laccase-gadolinium phosphate hybrid nanoparticles (laccase@GdPO4·HNPs) and enzyme mediator with an antibiofilm property coated on the surface of the ETT. The hybrid nanostructures were fabricated through a simple, rapid, and facile laccase immobilization method, resulting in efficiency and yield percentages of 82 ± 6% and 83 ± 5%, respectively. The surface of the ETT was then functionalized and coated with the constructed HNP/catechol. The layered ETT was able to reduce the surface adhesion of Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus by 82.1%, 84.5%, and 77.1%, respectively. The prepared ETT did not affect the viability of human lung epithelial cells L929 and A549 at concentrations of 1-5 mg mL-1. The layered ETT produced a strong computed tomography (CT) signal in comparison with iobitridol. The HNP/catechol-coated ETT exhibited a Gd3+ release of 0.45 ppm over 72 h, indicating reduced risks of cytotoxicity arising from the metal ions. In this research we develop a biofilm-resistant and contrasting agent-based ETT coated with green synthesized laccase@GdPO4·HNPs.

Efficient biocatalytic removal and algal detoxification of Direct Blue-15 by the hierarchically structured, high-performance, and recyclable laccase@yttrium phosphate hybrid nanostructures.

From the environmental point of view, azo dye industrial effluent is a major public health concern due to its toxic, carcinogenic, and teratogenic characteristics. On the other hand, using enzyme-based technologies offers a promising systematic and controllable method for removing synthetic dyes from wastewater. In the present study, yttrium (Y3+) phosphate was applied for the synthesis of hybrid nanoparticles (HNPs) consisting of laccase as the green catalyst. When the association of HNPs was fixed by glutaraldehyde (GA), three-dimensional cubic structures with the regular arrangement were provided. GA increased the reusability of the fabricated hybrid nanostructures (HNSs) up to 32 successive cycles. About 85% of Direct Blue-15 was removed after a 4 h-treatment using laccase@YPO4•HNPs and laccase@GA@YPO4•HNSs. The azo dye removal data were well-fitted with a pseudo-second-order model for both types of the prepared HNSs. For the model freshwater green alga Raphidocelis subcapitata, the half maximal effective concentration (EC50) of the dye decreased 10- and 100-fold after the removal with laccase@YPO4•HNPs and laccase@GA@YPO4•HNSs, respectively. GA-treated HNSs (250 U L-1) inhibited the biofilm formation by approximately 78%, 82%, and 79% for Escherichia coli, Staphylococcus aureus, and Bacillus subtilis, respectively. Thus, the fabricated laccase@GA@YPO4•HNSs could be presented as a novel, efficient, and recyclable heterogeneous biocatalyst for wastewater treatment and clean-up.